ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

With the rapid rise of large language models(LLM),the natural language generation capabilities of deep learning have demonstrated significant value in the medical field.However,the"closed nature"of model parameters makes them prone to generating"hallucinations",making it difficult to provide accurate answers to the latest knowledge,and the reasoning process lacks transparency and traceability.Retrieval-augmented generation(RAG)technology addresses these issues by actively connecting external information sources such as document databases and knowledge graphs during the generation process.This significantly reduces the dependence of LLM on outdated training data and introduces verifiable evidence and real-time knowledge updates into their responses.In the medical field,RAG technology effectively addresses the high-accuracy and traceability requirements of literature retrieval and clinical decision support.It is widely applied in areas such as drug discovery,pharmacovigilance,and the diagnosis and treatment of rare diseases.By integrating emerging technologies such as reinforcement learning,multimodal processing,and compliant privacy protection,RAG technology is evolving towards a more open and highly customizable direction,providing innovative intelligent solutions for medical information retrieval and decision-making support.

The cultivation of innovation ability is not only the essential requirement of graduate education,but also the strate-gic demand of the development of the communist party and our country,and is of great significance to the realization of the Chinese dream of the great rejuvenation of the Chinese nation.Curriculum ideology and politics should run through the whole process of post-graduate innovation ability training.However,the curriculum ideology and politics and postgraduate innovation ability training lack deep integration.It's important for postgraduates'growth and scientific research innovation that the curriculum ideology and politics covers the whole process of scientific research activities.Therefore,this paper focuses on the design and specific implementation schemes of the curriculum ideology and politics on the postgraduate innovative ability training at the respiratory disease research team in the department of medical immunology.It makes a basis for optimizing postgraduate curriculum ideology and politics teaching in the future,which also provides ideas for cultivating innovative talents with both morality and ability in medical specialty.

In recent years, minimally invasive surgical techniques, especially laparoscopic and robot-assisted surgery, have fundamentally changed the standard procedure for living donor liver retrieval and are gradually expanding into the core area of recipient surgery. This review systematically examines the latest advancements in the application of minimally invasive techniques in surgery for liver transplant recipients, focusing on the current status of the integrated application of innovative technologies such as laparoscopy, robot-assisted surgery, and magnetic anastomosis. In addition, this article delves into the potential and evidence-based basis for improving postoperative recovery and reducing surgical complications, and analyze the technical complexity, ethical considerations, equipment dependence, and training challenges faced in achieving full minimally invasiveness in key stages of donor liver implantation. Lastly, the future development directions are discussed, emphasizing that innovation in technological instruments, establishment of standardized training systems, deep multidisciplinary integration, and assemblage with emerging technologies are key pathways to safely and efficiently advance this field, ultimately aiming to provide optimized surgical treatment options for more patients with end-stage liver disease.

Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

Recently， Asian Pacific Association for the Study of the Liver published the recommendations for the diagnosis and management of non-cirrhotic portal fibrosis （NCPF）/idiopathic portal hypertension （IPH）. The guidelines mainly elaborate on the definition， diagnosis， histological features， natural history， and management of NCPF/IPH， in order to strengthen the understanding of NCPF/IPH-related issues and establish a global consensus. This article makes an excerpt of the key statements in the guidelines.

This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans ; Computational Biology ; Diabetic Nephropathies/physiopathology* ; Protein Interaction Maps ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Phagocytosis/genetics* ; Efferocytosis

OBJECTIVES: To create a mixed valvular heart disease (MVHD)-related age-adjusted comorbidity index (MVACI) model for predicting mortality risk of patients with MVHD. METHODS: A total of 4080 patients with moderate or severe MVHD in the China-VHD study were included. The primary endpoint was 2-year all-cause mortality. A MVACI model prediction model was constructed based on the mortality risk factors identified by univariate and multivariate Cox regression analysis. Restricted cubic splines were used to assess the relationship between MVACI scores and 2-year all-cause mortality. The optimal threshold, determined by the maximum Youden index from receiver operator characteristic (ROC) curve analysis, was used to stratify patients. Kaplan-Meier method was used to calculate 2-year all-cause mortality and compared using the Log-rank test. Univariate and multivariate Cox proportional hazards models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI), evaluating the association between MVACI scores and mortality. Paired ROC curves were used to compare the discriminative ability of MVACI scores with the European System for Cardiac Operative Risk Evaluation Ⅱ(EuroSCORE Ⅱ) or the age-adjusted Charlson comorbidity index (ACCI) in predicting 2-year clinical outcomes, while calibration curves assessed the calibration of these models. Internal validation was performed using the Bootstrap method. Subgroup analyses were conducted based on etiology, treatment strategies, and disease severity. RESULTS: Multivariate analysis identified the following variables independently associated with 2-year all-cause mortality in patients: pulmonary hypertension, myocardiopathy, heart failure, low body weight (body mass index <18.5 kg/m²), anaemia, hypoalbuminemia, renal insufficiency, cancer, New York Heart Association (NYHA) class and age. The score was independently associated with the risk of all-cause mortality, and exhibited good discrimination (AUC=0.777, 95%CI: 0.755-0.799) and calibration (Brier score 0.062), with significantly better predictive performance than EuroSCORE Ⅱ or ACCI (both adjusted P<0.01). The internal validation showed that the MVACI model's predicted probability of 2-year all-cause mortality was generally consistent with the actual probability. The AUCs for predicting all-cause mortality risk were all above 0.750, and those for predicting adverse events were all above 0.630. The prognostic value of the score remained consistent in patients regardless of their etiology, therapeutic option, and disease severity. CONCLUSIONS The MVACI was constructed in this study based on age and comorbidities, and can be used for mortality risk prediction and risk stratification of MVHD patients. It is a simple algorithmic index and easy to use.
Humans ; Prognosis ; Comorbidity ; Heart Valve Diseases/epidemiology* ; Female ; Male ; Middle Aged ; Aged ; Proportional Hazards Models ; Risk Factors ; China/epidemiology* ; Age Factors ; Risk Assessment ; Adult ; ROC Curve

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Shengjiangsan is a classic formula for treating warm diseases with wide clinical application and accurate efficacy. There are different opinions on the origin of this formula and lacks key information research on this formula. Therefore， in this study， we conducted systematic research into the historic origin， composition， and other key information of this Shengjiangsan. Results showed that Shengjiangsan has different versions， with "Neixian Fufang"， "Jiawei Jianghuangwan"， "Peizhensan"， and "Taijiwan" being the same formula with different names. Shengjiangsan was first recorded as "Neixian Fufang" in Wanbing Huichun written by GONG Tingxian from the Ming dynasty， inherited and developed by YANG Lishan from Qing dynasty， and has been passed down to modern times. Pills and powder are two main forms of Shengjiangsan， and powder has become more popular nowadays. According to the measurement system of Ming and Qing dynasties， the recommended dosage and usage of Shengjiangsan are as follows. For the pill version of Shengjiangsan， Bombyx Batryticatus of 74.6 g， Curcumae Longae Rhizoma of 9.325 g， Cicadae Periostracum of 9.325 g， and Rhei Radix et Rhizoma of 149.2 g were processed into pills for preparation. Single dosage is Bombyx Batryticatus of 1.15 g， Curcumae Longae Rhizoma of 0.14 g， Cicadae Periostracum of 0.14 g， and Rhei Radix et Rhizoma of 2.3 g， with halved dosage applied for children. For the powder version of Shengjiangsan， the dosage varied in accordance with the severity of the disease. Bombyx Batryticatus of 1.84 g， Curcumae Longae Rhizoma of 0.28 g， Cicadae Periostracum of 0.92 g， and Rhei Radix et Rhizoma of 3.68 g were processed into powder for patients with mild symptoms. Bombyx Batryticatus of 2.48 g， Curcumae Longae Rhizoma of 0.37 g， Cicadae Periostracum of 1.23 g， and Rhei Radix et Rhizoma of 4.91 g were processed into powder for patients with severe symptoms. Bombyx Batryticatus of 3.68 g， Curcumae Longae Rhizoma of 1.84 g， Cicadae Periostracum of 0.55 g， and Rhei Radix et Rhizoma of 7.36 g were processed into powder for patients with critical conditions. In this formula， four herbs were ground to fine powder. For patients with mild symptoms， the whole formula was divided into four dosages， and each dosage weighed 6.71 g. The 200 mL yellow rice wine and 18.65 g honey were added， and the solution was stirred and taken cold till full recovery. For patients with severe symptoms， the whole formula was divided into three dosages， and each weighed 8.95 g. 300 mL yellow rice wine and 27.98 g honey were added， and the solution was stirred and taken cold. For patients with critical conditions， the whole formula was divided into two dosages， and each weighed 13.43 g. 400 mL yellow rice wine and 37.3 g honey were added， and the solution was stirred and taken cold. Shengjiangsan has the effect of ascending lucidity and descending turbidity， dissipating wind， and clearing heat. It is specialized in treating severe heat in exterior， interior， and triple energizers in warm diseases and has a wide modern clinical application. In this study， the historic evolution and key information of Shengjiangsan were reviewed and analyzed， and the key information table of Shengjiangsan was attached， serving as a reference for scholars' research and a theoretical basis for its market transformation.